Animal healthcare, well-being and nutrition

ABSTRACT

Dynamic management of the health care, nutrition and well-being of pet animal, such as a dogs and cats. Data relating to the species of the animal, a selected group of the species, and the animal, including diagnostic laboratory test data of the animal are related by a computer. A management regimen for the animal is based on this. Updating the data picks up drifts in different populations of the animals, groups and species over time to enhance the management.

RELATED APPLICATIONS

This application is a continuation of U.S. application Ser. No.09/898,193 filed on Jul. 2, 2001 now U.S. Pat. No. 6,537,213 which is acontinuation in part of U.S. application Ser. No 09/432,85 1 filed Nov.2, 1999 now U.S. Pat. No. 6,287,254 which is a continuation in part ofU.S. application Ser. No 09/419,192 filed Oct. 15, 1999 now U.S. Pat.No. 6,730,023. The contents of these applications are incorporated byreference herein.

TECHNICAL FIELD

This invention is concerned with animal health diagnosis. Moreparticularly the invention is directed to the testing, diagnosis andprediction of diseases and disorders of animal companions, for instancedogs and cats.

Further this invention relates to a method, system and apparatus for themanagement of comprehensive and cumulative genetic and health assessmentdatabases in relation to animals worldwide. In particular, the inventionrelates to a bioinformatics system and its implementation in relation toanimal biological data.

More specifically the invention is directed to animal health care,well-being and nutrition, and methods and systems for enhanceddetermination of these factors.

BACKGROUND OF THE INVENTION

Breeders, owners, and caregivers of animals which can be companions,such as dogs, cats, horses, farm, food, or zoo animals, and wildlife,have a need to understand their physical and biological attributes,genetic makeup, heritable disease, and disorder background, andlongevity.

Substantial investments in time, effort and financial resources are madeby the breeders, owners, and caregivers of these animals, particularlypurebred animals, to characterize their health state and predict theirmorbidity, mortality and longevity. Resources are separately directed toobtaining information about their genetic background. There is also aneed to conduct periodic comprehensive health assessments of animals.

The probability that an individual animal will develop a specifichealth-related condition in its lifetime is a product of complexinteractions between its genetic makeup, environmental influencesincluding diet, and agents of disease (e.g., chemical, physical, orbiological) that it encounters. Perhaps the best indicator of overallhealth of an individual animal or breed is longevity.

The physical attributes, and other descriptive and health assessmentinformation is generally termed in this application as the phenotypicinformation. Genetic disorder information is termed in this applicationas the genotypic information. Generally, these are two distinct anddiffering sets of information.

Phenotype Data

The physical descriptive and health assessment profiles includecharacteristics such as the physiological, pathological,endocrinological, hematological, epidemiological, behavioral, andimmunological data from parameters such as phenotype, breed, lifespan,health history, and presence of infectious diseases and metabolicdisorders. All of this is part of the phenotypic information. A healthassessment profile of an animal typically relates to a particularsubject of the group, as opposed to the group of animals as a whole.Generally, the phenotype is the genetic nature of an organism that isrevealed by visible characteristics or measurable performance, incontradistinction to the genotype, which may not be evident without abreeding test or genetic map.

Laboratories having a central database processing resource (CDPR) aswell as in-office laboratory equipment at veterinary hospitals orclinics are used for analyzing blood and other biological samples of asubject animal. This is a system for obtaining the phenotypicinformation. Communication systems are known for connecting theselaboratories with veterinary clinics through a telephone and/or faxconnection on an automated basis. These systems permit the veterinarian,animal hospital, or other authorized person (collectively orindividually termed the “remote user”) to receive the health assessmentprofile and basic descriptive identifying data, namely phenotypicinformation, of a subject animal from the CDPR. Until recently, it wasnot possible for the remote user to access the CDPR directly to obtainthis phenotypic information of a subject animal.

It is known for the breeder and/or owner of animals, such as purebredcompanions in the nature of dogs, cats, and horses, or animals of mixedbreeding, to obtain health assessments of their animals. The ownersobtain these data by submitting blood or other body fluid and tissuesamples of their animals, usually through a veterinarian or veterinaryclinic, to a laboratory for analysis of the biological, physiological,or pathological condition, namely the physical health of the animal.These data are then reported to the owner through the veterinarian orveterinary clinic. The data also can be stored on the CDPR of thelaboratory. Additionally, for each subject animal, the phenotypic datacan be stored on a computer storage system at the veterinary clinic orin a computer storage system of the owner and/or breeder. The retrievalof the data can be electronically, by voice, hard copy, or fax asrequired.

Seeking, obtaining and storing this phenotypic information is driven bythe needs of the animal breeder, owner or the agent of the owner and theanimal's healthcare provider. This information is of a nature that it isthe primary information sought to resolve the clinical, diagnostic,management, and therapeutic needs of an animal subject when the animalis in need of periodic wellness examination, is ill, or is to berestored to a well condition. These data are the essential informationresorted to by the clinician in the care of animals.

Genotype Data

The genotypic information relates to genetic mapping, geneticbackground, and genetic screening databases. This includes data obtainedfrom the pedigree, family history, heritable physical characteristics,genetic screening tests, DNA testing, genomic mapping, and relatedlaboratory assessment of the gene product for known or suspectedcongenital and heritable traits. In this application, the term “geneproduct” means the specific phenotypic characteristic(s) resulting fromthe expression of the genotype, and may include certain specificlaboratory test data.

This second aspect of data associated with the animals is the genetic orgenotype data or information. These data are typically used to estimatethe presence and prevalence of disease or disorder among differentbreeds or kinds of animals. These data are currently available on someselect clinical research databases, in book form, hard copy, or ingenetic disease registries.

When retained in a genetic disease registry, the data typically listonly those animals that are not affected with or carrying the heritabletrait in question. The abnormal or non-normal conditions (affected withor carriers of the heritable trait) are normally the subject ofconfidential knowledge of a breeder and/or owner, and not the subject ofa generally accessible database. This is retained as confidential by theowners either for financial reasons, risk reasons, legal liabilityreasons, or personal reasons.

The genotypic information typically relates to individual animals, or agroup or class of animals and is most often stored manually in anon-CDPR facility. It is not typically stored by veterinarians in aclinical setting, since the genotypic data is a specialist form of dataused mainly for cataloging and research of diseases and disorders amonganimals. It is also not generally available for access to assist in theclinical analysis, diagnosis, and therapeutic management of animals.

This genotypic information, namely the physical characteristics andgenetic makeup (pedigree), heritable disorder history, and relatedhealth history of animals in the group is usually manually recorded bybreeders, owners, and researchers of companion and other valued animals.The genetic constitution of an organism includes genes without visibleeffects as well as those revealed by the phenotype. It may refer to allthe genes or to a single pair of alleles. The genotypic information istransmitted manually to and from persons or local and national genotypicdatabases maintained for specific disorders, and designed to fosterresearch into diseases and disorders, rather than being readilyaccessible to users for clinical purposes in the manner of phenotypicdata on a CDPR.

Some of the genetic data are available on registries related to specificdiseases or disorders, for instance, hip dysplasia, eye conditions,thyroid conditions, and blood conditions. Such disease-specificregistries are usually set up either by identifying affected animalbreeds, or are indexed by disease or disorder. The genetic informationdatabases are generally closed (kept confidential), but in some casesmay be open to researchers or members of groups, associations, andclubs.

Failings of the Existing Systems

To promote better health among animals, which can be animal companions,sport animals, farm animals, and the like, such as canine, feline,equine, bovine, porcine, caprine, ovine, and zoo animals or wildlife, itis important to secure accessible genotypic or genetic informationdatabases. It is also important to be able to relate these genotypicdatabases to the health assessment profiles or phenotypic databases ofparticular subject animals.

Many purebred animals are valuable, and so it is important to obtaintheir descriptive phenotypic information, and periodic health assessmentdata throughout their lives, and also to incorporate their genotypicinformation in order to promote and maintain effective high quality andhealthy breeding stock, and maximize their lifespan. The phenotype datafor an animal include the health assessment profile, breed, and thephysical characteristics of the animal. The genotype data include thegenetic map, pedigree, family history, genetic screening tests, anddisorder and disease characteristics of a particular animal, animalfamily, line, or group of animals.

There is a need to develop these data in a cumulative, comprehensive,and dynamic system of database management to thereby enhance the healthpredictability, and longevity of animals.

This type of comprehensive and cumulative database on individual orgroups of animals needs to be preserved and shared locally, regionally,nationally, and globally. A mechanism to do this is presently not knowndue to the various constraints surrounding each of the two types ofdatabases. The phenotype database storage, use, and access is fashioned,formed and structured for use by clinical laboratories andveterinarians. The genotype information is fashioned and structuredgenerally for clinical research and breeder/owner uses as opposed toclinical medical uses.

It is not known to store and/or present phenotypic information andgenotypic information as a comprehensive and cumulative assessment ofindividual animal subjects, families of subjects, breeds of subjects, orspecies of animals in a computerized format which is available throughcomputer networking to authorized remote users.

Accordingly, there is a need to relate different databases from animals,animal groups or species, in a manner to permit enhancement of theanimal kingdom for breeding and growth in a healthy manner with aminimum of disease (reduced morbidity and mortality) and increasedlongevity.

As the above demonstrates, there is a need for a new database managementbioinformatics scheme and relational database, together withcomputerized networks that manage, analyze, and/or integratecomprehensive and cumulative animal health assessment data and geneticidentifier, genomic mapping, and genetic assessment data. Acomprehensive approach to animal health and genetic selection ormanagement of animals, and their clinical care is the subject of thepresent invention.

Current laboratory and research systems and computerization have notachieved this, and nor have communication protocols been usedeffectively in this technological area to facilitate such a relationshipor relational bioinformatics database system for management anddissemination of this comprehensive and cumulative information.

More specifically, it is necessary in animal health diagnosis and carethat appropriate predictive testing for diseases and disorders ofanimals be achieved in order to reduce morbidity and mortality, andimprove the quality of life and lifespan. Currently this is not done inrelation to the health assessmant data of an animal together with thegenetic data related to that same animal. Current tests do not provideas much data as possible to attain correct diagnosis and disorderpredictions with the net result of an improvement in the quality of lifeand increased longevity. Moreso, currently available testing isunnecessarily complex and expensive in relation to the ability to be anaccurate predictor of diseases and disorders in animals, and hence theirlikely longevity.

SUMMARY OF THE INVENTION

The invention is directed to a method, apparatus and system ofobtaining, analyzing and reporting laboratory test data in relation tothe health assessmant data of an animal together with the genetic datarelated to that same animal.

These data include a panel of tests related to at least one of endocrinefunction, immunologic function, gastrointestinal function andnutritional analysis, inborn errors of metabolism, paternity, DNAfingerprinting, hemostasis and coagulation function, vaccinal antibodystatus, adverse and potential adverse vaccine reaction, infectiousdiseases, pathology, blood typing and bone marrow analysis, cellcytotoxicity, cytokine and allergy testing, and markers of neoplasticand paraneoplastic change. These data are relevant to the likelymorbidity, likely longevity, and/or the potential risk for disease ordisorder for the animal.

According to one aspect of the invention, health profiling of an animalis effected to determine characteristics related to the temperament ofthe animal which impacts on its longevity. Biological laboratory testdata from a bodily fluid or tissue of an animal are analyzed. Such testdata relate to the level of neurotransmitter activity of the animal. Thedata relate to at least one of the value of serotonin, thegamma-aminobutyric acid (GABA), the dopamine, the norepinephrine, thehistamine, or the other neuropeptides of the animal. The value shouldfall within predetermined levels as a predictive determinant of theanimal's temperament (passivity, assertiveness, or aggressivity).

One other aspect of the invention relates health profiling of an animalto determine characteristics related to at least one of the immunestimulation reaction, evidence of neoplastic or paraneoplastic change,or the cellular inflammatory response of the animal. Biologicallaboratory test data from a bodily fluid or tissue of an animal areanalyzed. The test data relates to at least one of cell cytotoxicitymarkers, cytokine and chemokine levels, immunoglobulin levels, type andamount of lymphocyte subsets and lymphocyte markers, and markers ofneoplastic or paraneoplastic change of the animal. The value should fallwithin predetermined levels as a determinant of the immune stimulationreaction, neoplastic or paraneoplastic change, or the cellularinflammatory response.

According to another aspect of the invention, health profiling of ananimal determines characteristics related to inherited organ dysfunctionor dysplasia of the animal, at least one of which is neuronal,neuromuscular or renal. Biological laboratory test data from a bodilyfluid or tissue of an animal are analyzed. The test data relate to anamino acid, carbohydrate, lipid or other metabolic component, body fluidor tissue marker of the animal. The data includes obtaining data relatedto at least one of the value of the methyl malonic acid, thefucose-containing cell metabolites, uric acid, normoglycemic glycosuria,amino acid uria, mannosidase containing cell metabolites, amyloiddeposition in tissues, neuronal ceroid lipofuscin deposition, anddeposition of gangliosides and other lysomal storage substrates of theanimal. The value should fall within predetermined levels as adeterminant of the inherited organ dysfunction or dysplasia.

According to a further aspect of the invention, health profiling of ananimal determines characteristics related to autoimmune thyroiditis ofthe animal. Biological laboratory test data from a bodily fluid ortissue of an animal are analyzed. The test data relate to a physiologicor genetic marker for automimmune thyroiditis of the animal. The datarelates to at least one of the results of a comprehensive thyroidautoantibody test profile, DNA fingerprint (the gene map), and markersfor immunoglobulin receptors on B-cells, T-cell receptors, and proteinproducts of the major histocompatibility complex (MHC) genes (Class Iand II allellic HLA, DLA or equivalent antigenic specificities) of theanimal. Example assays to screen for MHC genes include restrictionfragment length polymorphism (RFLP), polymerase chain reaction (PCR)RFLP, PCR sequence-specific oligonucleotides (SSO) and PCRsequence-specific primers (SSP). The values should fall withinpredetermined levels as a determinant of auto immune thyroiditis.

According to a further aspect of the invention, health profiling of ananimal determines characteristics related to presence of orsusceptibilty to mammary cancer of the animal. Biological laboratorytest data from a bodily fluid or tissue of an animal are analyzed. Thetest data relate to estrogen (estradiol-17β), estrogen receptors,interleukin (IL) 6, progesterone, and progesterone receptors. The valueshould fall within predetermined levels as a determinant of presence orsusceptibilty to mammary cancer.

According to a further aspect of the invention, health profiling of ananimal determines characteristics related to the tissue environment ofthe eye and brain (ocular and blood-brain barrier) which are sitesprotected from the normal immunologic surveillance mechanisms.Biological laboratory test data from a bodily fluid or tissue of ananimal are analyzed. The test data relate to the soluble and cellularimmune inflammatory response mediators (cytokine and chemokine levels,immunoglobulin levels, and lymphycyte susbset markers). The value shouldfall within predetermined levels as a determinant of integrity ofprotected immune surveillance mechanisms.

According to a further aspect of the invention, health profiling of ananimal determines characteristics related to the tendency to bleedexcessively are determined. Biological laboratory test data from abodily fluid or tissue of an animal are analyzed. The test data relateto a comprehensive assessment of the hemostatic and coagulationfunction. The value should fall within predetermined levels as adeterminant of the presence of bleeding disorder.

The invention includes obtaining genetic data related to the animal, andrelating the genetic data related to that animal with the biologicaldata. Also the profiling includes obtaining data related to the currenthealth condition of the animal.

More particularly the invention comprises combining genetic data ofanimals with health assessment data of animals thereby to permit ananalysis predicting health, disease and disorder probabilities andlongevity of selected animals. The combination is analyzed, and a reportis provided to a remote user based on the analysis the health assessmentdata of the animal and the genetic data.

In light of the above, there is provided by this invention a system formanaging animal diagnosis, including the performance of specific tests.The phenotypic and genotypic data and information relating to animals,particularly purebred animals can be used to enhance the prediction ofdisease and/or disorder.

The invention also provides a bioinformatics system for inputting,controlling, analyzing and outputting of a broad range of criteriarelated to the health, genetic background and longevity of animals. Thisincludes a system concerning phenotype data and genetic data relating toanimals. Further, there is provided a system for screening of geneticdata and genomic mapping, and integrating the phenotype healthassessment data and genetic identifier and assessment data in a CDPR.Moreover, there is provided a system for analyzing the health assessmentor phenotypic data with the interrelated genetic or genotypic data.Thereafter, those data and analyses are communicated from the CDPR in abroad range and in a manner that has not previously been possible.

The present invention offers a unique solution to above-describedproblems by providing an apparatus, method and system, in relation toanimals, for performing data analyses of biological specimens fromspecific subject animals or animal groups in relation to specificsubject animal or animal groups of genetic data. The apparatus, methodand system comprises a controller for obtaining, inputting, andanalyzing biological, physiological, and pathological test data togetherwith genomic mapping and genetic screening data into the CDPR.

The biological, physiological, and pathological data of the subjectanimal or animal group and the genetic data of the subject animal oranimal group are communicated to a remote user as raw data or asrelated, analyzed biological, physiological, and pathological data andgenetic data. The remote user can also appropriately access the CDPR toinput data to, or obtain data from, the CDPR.

The CDPR includes at least two databases, one of the databases containsgenetic information in relation to animals and the other is a phenotypicdatabase.

The genetic database is either a specific file of a selected animal or ageneralized animal database relating to group characteristics, and iscross-relatable with the phenotypic database of particular selectedsubject animals.

Additionally other databases can be used and cross-related to thesedatabases. The genetic database includes data from selected animals,animal families, animal breeds and/or data related to selected animaldiseases and/or disorders. Other databases include those related togenetic markers or maps of animals, databases related to epidemiology,purebred animal ownership, identification registries, and studbookregistries.

The phenotype, health profile, or health assessment database containsdata which is mostly phenotypic. The genotype database includes datawhich is in the category of mostly genotype or genetic and which mayinclude a second category of some phenotype data which predicts ormanifests the genotype and genetic data. The invention includes relatingthe phenotypic data to either one or both types of the genotypic data.

Information in the databases are used to build computer drivenstatistical models to predict the occurrence of specific diseases andlongevity for individual animals on a breed-by-breed or family and groupbasis. Multivariate statistical techniques are used including multipleregression, logistic regression, and Cox proportional hazards. As newdiagnostic technology and genomic information become available, thedatabase is continually expanded and the statistical models are updatedto enhance predictive ability. This ability to predict the occurrence ofdisease or disorder is used to develop and evaluate screening programsin veterinary medicine in order to detect disease earlier, therebyimproving the outcome and quality of life for animals and their owners.The information is also used to design disease prevention programs basedon dietary/environmental modification and selective breeding. Thedatabase is also used to explore previously unsuspected relationshipsbetween specific diseases such as cancer and diet, vaccination, orchemical exposures.

According to a further aspect of the invention there is a dynamic methodand system of managing the health care and well-being of a non-livestockpet animal subject. Such an animal is preferably a canine subject or afeline subject. This method comprises:

-   -   a) obtaining a data base relating to at least one of:        -   i. the species of the animal subject,        -   ii. a selected group of the species;    -   b) obtaining data relating to the subject, the data including        laboratory test data relating to the subject;    -   c) relating the database of a) with the data of b) by a        computer; and    -   d) determining, based on c), a regimen for the management of the        subject.

The healthcare and well-being could include the nutrition management orthe health management or the lifestyle management.

The data base of the selected group of the species is at least one ofbreed, age, sex, size, weight, performance use, or geographicallocation.

The nutritional regimen is at least related to the nutrient or caloriccomposition, or the food allergies and food intolerances. Thetherapeutic intervention or maintenance is at least one of drugs,nutraceuticals, or holistic treatments, exercise or liquid intake. Thediagnostic laboratory test data is a comprehensive general healthprofile and selectively at least one selected diagnostic profile for aselected subject. Preferably the laboratory data for the subject isobtained over time from the same laboratory. This likely to enhance theuniformity of the data, and render the determinations more accurate, andpredictive of health, nutritional requirements, temperament, andlongevity.

The computer is at least one of an expert system or interrelationshipprogram or network for determining data base and data relationships.This can be a system such as a neural network, or other statisticalsampling systems and networks.

The database of at least one of the species or the group is periodicallyupdated thereby to obtain cumulative data of the species or group.Preferably both these data bases are used, and preferably both areupdated to obtain the cumulative data. The data of the subject isperiodically updated thereby to obtain cumulative data. Preferably, boththe databases are periodically updated. The updating picks up data driftin different populations of the subjects, groups and species over time,and thereby allows for the regulation of the database so as to besubstantially or essentially current.

By having this feature there is obtained a method and system whichprovides for enhances healthcare and well-being management of thesubject. Thus the data of the subject is compared to substantially oressentially current data. Similarly by retaining a history of thesubject data and relating this to the updated databases, the accuracywith which the healthcare and well-being is managed is significantlyenhanced.

The invention also includes the step of reporting the determination ofthe health care, well-being, nutrition or other therapeutic requirementsand suggestions or health on a communications network including theInternet. Preferably, there is a payment procedure for the report whichis achieved through the Internet. This communication network andstructure is described here in further detail.

There is provided means for inputting data into the genetic database andphenotypic database, and other databases, storing the data in thesedatabases, analyzing the data in a relational sense from the differentdatabases, and retrieving the data from these databases, namely thedatabases which are part of the CDPR.

A further aspect of the invention is the accessibility of the healthassessment database and/or genetic database or other databases of theCDPR by the remote user selected on the basis of password, securitycontrol, and financial payment such that the data can be transmittedinto and from the CDPR by a computer network. Use of selected passwords,encryption systems, and payment systems are employed to facilitate andrestrict the flow of data in and/or out of the databases. Alerts can beset up to advise of attempts at unauthorized access to the CDPR. Thecomputer network may conveniently include the Internet.

As required, the data in the CDPR can also be distributed to multipleauthorized remote parties, namely third parties for research or otheranalysis. The invention also includes a method and system for achievingthis.

Further aspects of the present invention will become apparent in thecourse of the following description and by reference to the attacheddrawings.

BRIEF DESCRIPTION OF THE DRAWINGS

FIG. 1 is an overall view of a web-based system to provide access to adatabase management system of an animal genetic database and a healthassessment database of the invention, in relation to the Internet.

FIG. 2 is a graphical illustration of a computer network, namely theInternet.

FIG. 3 is a block diagram of an exemplary computer system for practicingvarious aspects of the invention.

FIG. 4 is a view of a browser for the database management system foraccessing an animal genetic database and a health assessment database ofthe invention.

FIG. 5 is a basic flow diagram illustrating an exemplary process bywhich an operator of a CDPR receives and transmits data relating tohealth assessment and genetic information.

FIG. 6 is a detailed flow diagram of the system steps employed in oneembodiment of the present invention wherein a remote user accesses andoutputs data.

FIG. 7 is a detailed flow diagram of the methods and steps employed by aremote user to add data to the database.

FIG. 8 is a flow chart illustrating an exemplary process by which thelaboratory dynamically contributes, transmits and receives dataassociated with health assessment and genetic data to the CDPR.

DETAILED DESCRIPTION OF THE PREFERRED EMBODIMENT

The present invention will now be described in detail with reference toa few preferred embodiments thereof, as illustrated in the accompanyingdrawings. In the following description, numerous specific details areset forth in order to provide a thorough understanding of the presentinvention. It will be apparent, however, to one skilled in the art, thatthe present invention may be practiced without some or all of thesespecific details. In other instances, well known process steps have notbeen described in detail in order to not unnecessarily obscure thepresent invention.

Genetic Screening and Counseling of Purebred Animals

The common practice to line-breed and inbreed purebred animalsfacilitates the transmission and recognition of congenital and heritabledefects. Large-scale screening programs for the identification ofgenetically affected and carrier animals are an effective way todiscover and eventually control the frequency of these defects withinthe population at large. Screening programs of this type have been usedsuccessfully in humans for many years (e.g. Tay-Sachs disease,phenylketonuria) and more recently have been applied to animals (e.g.mannosidosis in cattle; hip dysplasia, eye, blood and heart diseases indogs). Genetic screening may be essential to the survival of breeds inwhich mild or moderately severe defects have been propagated unknowinglyfor many generations.

It is important that the top-producing sires and foundation dams of abreed be screened for conditions prevalent in that breed or in thespecies generally, because they represent the major nucleus of geneticmaterial for the current and future decades. Most purebred animalsraised today have evolved over the years from a relatively small genepool. Even though a particular genetic disorder may initially have beenrecognized in a specific line or family within a breed, all importantbreeding stock of the breed need to be screened because their similargenotype evolved from the original restricted gene pool. If thisapproach is not taken, the frequency of genetic defects in the breedwill inevitably increase and have a negative impact on overall healthand longevity.

Depending on the mode of inheritance, different approaches may need tobe applied for the detection and control of genetic disorders. It isadvantageous to be able to select against heterozygotes (carriers)rather than have to eliminate affected individuals from a breedingprogram once the condition is manifested. Control and elimination of thedisease by testing are feasible and reliable in cases where theasymptomatic or carrier state has an expressed phenotypic, biochemicalmarker (e.g., as measured in a blood, urine or saliva test,electrocardiogram, skin biopsy, eye examination, or hair analysis). Somecurrent examples include testing for bleeding disorders like vonWillebrand disease and hemophilia; autoimmune thyroid disease leading tohypothyroidism; the various eye, heart, metabolic enzyme and storagedisorders; and the bone and neuromuscular diseases. Coupled with thisapproach to eliminating undesirable traits is the necessity to evaluatebreeding stock regularly for overall soundness, reproductive health andperformance, and longevity.

Features Related to Genetic and Other Data Associated with Animals A.Physical Characteristics of Disease

In the early days when animal breeders began recognizing recurringsymptoms of disease states or physical characteristics, the undesirablefeatures of these traits led them to select away from the problems bytest mating and eliminating affected animals from the breeding pool.While this remains one way to select against inherited and congenitaldiseases, more reliable approaches have been implemented by screeningfor biochemical markers and most recently by using molecular genetictechniques.

A comprehensive worldwide database contains the following informationfor individual purebred animals:

Host characteristics: age, sex, neuter status, pedigree, height, weight,body mass index, coloration and markings, eye color, etc.

Diet: type and amount of dog and human foods consumed, vitamin andmineral supplements, frequency of feeding. This is used to derive thepercentage of calories derived from fat, carbohydrate, and protein.

Medical history: occurrence of diseases, infections, etc., includingdate of onset, treatment, duration, and outcome, cause of death andmethod of diagnosis; type and amount of medications used for treatmentor prevention of disease; type and frequency of vaccinations.

Personality and temperament: based on previously used personalityscales.

Laboratory data: consists of routinely collected blood, serum chemistrytests, urinalysis, etc., as well as laboratory tests performed to screenfor or diagnose specific conditions such as immune-mediated thyroiditis,hypothyroidism, cancer, etc.

Special diagnostic test results: include tests for hip dysplasia,congenital eye diseases, congenital heart diseases, blood disorders, andother suspected inherited disorders as tests become available.

Genetic information: derived from the canine genome project as well astests for specific inherited conditions such as progressive retinalatrophy, hemophilia, and von Willebrand disease.

B. Phenotypic Markers of Disease

While animal breeders (e.g., of purebred dogs) for the most part haveendorsed the long standing genetic screening programs for hip dysplasiaand blood and eye diseases, emphasis on other genetic disorders hasarisen, now that the major infectious, parasitic, nutritional andtraumatic diseases have been addressed and controlled to a large extentby modem veterinary medical practice. Furthermore, most animal fanciersbecome involved in breeding and showing their animals as a hobby ratherthan a prosperous enterprise as might apply to livestock or theperformance racing industry. The intense commitment to this hobby withits attendant social praise for the successful breeder and exhibitor,poses ethical dilemmas when prize-winning animals are identified ascarriers of a particular genetic disorder.

For about three decades, veterinary and comparative geneticists havedeveloped and relied upon physical and biochemical markers of specificgenetic traits to identify carrier and affected animals. These methodsaimed to produce reliable, practical, and affordable tests that would bepredictive of the gene product, and therefore the genotype of aparticular genetic disorder. To be considered accurate and predictive,retrospective analyses of data developed from these testing programswere compared to the pedigrees of animals being screened as a means ofvalidating the tests. Such genetic screening tests would be consideredreliable if they correctly identified animals as having the normal andabnormal genotypes at least 80% of the time.

An important indicator of overall health of an individual animal orbreed is longevity. Relationships between a specific health-relatedcondition and an animal's genetic, environmental influences and lifespanhave been characterized, in part, for several important diseases of dogsincluding bone cancer (osteosarcoma) and gastric dilatation-volvulus(GDV).

Osteosarcoma: The risk of osteosarcoma increases with increasing age,increasing weight and increasing height. Compared with the Germanshepherd breed, the highest risk of osteosarcoma occurs among large andgiant breeds, while small breeds have reduced risk. Furthermore, therisk of osteosarcoma is increased two-fold in neutered dogs.

GDV: Factors that increase the risk of GDV in purebred dogs are malegender, being underweight, eating only one meal per day, eating rapidly,and a fearful temperament. Factors that decrease the risk of GDV includea happy temperament and inclusion of table foods in the diet. Thelifetime risk of developing GDV in large and giant breed dogs is 20% and23%, respectively, whereas the lifetime risk of dying of GDV for thesebreeds is 6%.

Similarly, the comparative longevity of different dog breeds has beendescribed using the age of death and other descriptive characteristicsof more than 38,000 dogs that were included in a large veterinarydatabase. Predictable relationships were found between the breed andsize of dogs and the average age of death. It was noted that dogs areunique among animal species in having a more than 50-fold difference inadult body size and a corresponding large difference in longevitybetween the smallest and biggest dog breeds. Since these dog breeds havemore than 99% of their genome in common, it suggests that the geneticcode for both size and longevity is contained within a very small partof the dog's genome. As mapping of the canine genome progresses, itshould be possible to identify not only genes that code for specificdiseases such as cancer and GDV, but also for the genes that determinebody size and longevity.

C. Genotypic Markers of Disease

Recent advances in molecular genetics have focused on mapping the humangenome, and this has stimulated interest in developing parallel geneticmaps for animals. For example, it is estimated that a minimum of tenyears and several million dollars will be needed to map the caninegenome. Once developed, a genetic map provides information about therelative order and placement of genes or specific DNA markers onspecific chromosomes. This allows one to locate specific regions onchromosomes where genes of interest are likely to be found. Once amolecular marker is identified close to a specific gene of interest,screening tests for this particular marker can be used to identifyindividuals carrying or expressing the trait.

Other information in relation to genetic screening and health assessmentis contained in the literature references listed at the end of thespecification. The contents of these materials are incorporated byreference herein.

Some of the characteristics of animals with which this invention isconcerned are the following:

Genotype & Animal Mostly Mostly Some Phenotype Characteristics PhenotypeGenotype (Gene Product) Species X Purebred X Crossbred X Mixed breed XSize X Weight X Age X Sex X Lifespan X Body type X Color X Familyhistory X DNA testing X Genomic mapping X Blood type X Thyroid functionX von Willebrand factor X Hemophilia X Other bleeding disorders XGlucose X Cholesterol X Alkaline phosphatase X Alanine aminotransferaseX Bile acids X Cortisol X Cataracts X Progressive retinal atrophy XMicroophthalmia X Dry eye (KCS) X Hip dysplasia X Arthritis XTemperament X Ruptured cruciate ligament X Hemolytic anemia X UrinalysisX Kidney stones X Bloat (gastric dilatation) X Pyoderma X Seborrhea XSebaceous adenitis X Umbilical hernia X Inguinal hernia X Epilepsy XHeartworm disease X Cardiomyopathy X Patent ductus arteriosus XImmunoglobulin levels X

In the category of genotype and some phenotype, the phenotype component(measurable gene product) is typically less than 20%.

Diagnostic Testing

The development of one or more assays or techniques for performing theinvented testing protocols, standards and procedures of the presentinvention is straightforward, and within the knowledge of a personskilled in the art. The contents of U.S. Pat. No. 5,830,7009 (Benson)entitled “Detection Method for Homologous Portions of a Class ofSubstances” is indicative of some of the tests and formats that arepossible. The contents of that patent are incorporated by referenceherein.

One or more of a panel of tests relate to at least one of endocrinefunction, immunologic function, gastrointestinal function andnutritional analysis, inborn errors of metabolism, paternity, DNAfingerprinting, hemostasis and coagulation function, vaccinal antibodystatus, adverse and potential adverse vaccine reaction, infectiousdiseases, pathology, blood typing and bone marrow analysis, cellcytotoxicity, cytokines and allergy testing, and markers of neoplasticor paraneoplastic change. These data are relevant to the likelymorbidity, likely longevity, and/or the potential risk for disease ordisorder for the animal.

The following are some examples of diseases, disorders, and physiologicstates that use one or more of the diagnostic test panels set out below:

EXAMPLES Example 1 Temperament and Longevity

Characteristics related to the temperament of the animal which impactson its longevity are determined. Biological laboratory test data from abodily fluid or tissue of an animal are analyzed. Such test data relateto the level of neurotransmitter activity of the animal. The data relateto at least one of the value of serotonin, the gamma-aminobutyric acid(GABA), the glutamate, the dopamine, the glycine, the aspartate, theacetylcholine, the norepinephrine, the histamine, the substance P, thevasopressin, the vasoactive intestinal peptide, the neurotensin, or theother neuropeptides of the animal. The value should fall withinpredetermined levels as a predictive determinant of the animal'stemperament (passivity, assertiveness, or aggressivity).

Methods for measuring neurotransmitters are well known in the art.Neurotransmitters such as serotonin, epinephrine, norepinephrine,glutamate, and GABA can be measured by standard immunochemicaltechniques involving commercially available antibodies, eitherpolyclonal or monoclonal. Such antibodies are commercially availablefrom sources such as Sigma Chemical Company (St. Louis, Mo.). Theseimmunochemical techniques can involve either radioimmunoassay or otherwell-established assay techniques, such as ELISA (enzyme-linkedimmunosorbent assay). These neurotransmitters can also be measured bystandard non-immunochemical techniques such as gas chromatography.Neuropeptide neurotransmitters are preferably measured by immunochemicaltechniques.

Test panels Nos. 1, 2, 3, 8 and 10 set out below can be used to obtaindata for this Example 1.

Example 2 Immune Stimulation and Cellular Inflammatory Response

Characteristics related to at least one of the immune stimulationreaction, evidence of neoplastic or paraneoplastic change, or thecellular inflammatory response of the animal are determined. Biologicallaboratory test data from a bodily fluid or tissue of an animal areanalyzed. The test data relates to at least one of cell cytotoxicitymarkers, cytokine and chemokine levels, immunoglobulin levels, type andamount of lymphocyte subsets and lymphocyte markers, and markers ofneoplastic or paraneoplastic change of the animal. The value should fallwithin predetermined levels as a determinant of the immune stimulationreaction, neoplastic or paraneoplastic change, or the cellularinflammatory response.

Methods for measuring lymphokines and other cytokines are well known inthe art. These compounds are typically measured by immunochemicaltechniques using commercially available monoclonal antibodies or othermethods.

Test panels Nos. 1, 3, 4, 8, 9 and 10 set out below can be used toobtain data for this Example 2.

Example 3 Inherited Organ Dysfunction or Dysplasia

Characteristics related to inherited organ dysfunction or dysplasia ofthe animal, at least one of which is neuronal, neuromuscular or renalare determined. Biological laboratory test data from a bodily fluid ortissue of an animal are analyzed. The test data relate to an amino acid,carbohydrate, lipid or other metabolic component, body fluid or tissuemarker of the animal. The data includes obtaining data related to atleast one of the value of the methyl malonic acid, the fucose-containingcell metabolites, blood or urine urate or uric acid metabolites,normoglycemic glycosuria, mannosidase containing cell metabolites, aminoacid uria, amyloid deposition in tissues, neuronal ceroid lipofuscindeposition, and deposition of gangliosides and other lysomal storagesubstrates of the animal. The value should fall within predeterminedlevels as a determinant of the inherited organ dysfunction or dysplasia.

Test panels Nos. 1, 3, 5, 9 and 10 set out below can be used to obtaindata for this Example 3.

Example 4 Autoimmune Thyroiditis

Characteristics related to autoimmune thyroiditis of the animal aredetermined. Biological laboratory test data from a bodily fluid ortissue of an animal are analyzed. The test data relate to a geneticmarker for automimmune thyroiditis of the animal. The data relates to atleast one of the results of a comprehensive thyroid antibody testprofile, DNA fingerprint (the gene map), and markers for immunoglobulinreceptors on B-cells, T-cell receptors, and protein products of themajor histocompatibility complex (MHC) genes (Class I and II allellicHLA, DLA or equivalent antigenic specificities of the animal. Testassays to screen for MHC genes include restriction fragment lengthpolymorphism (RFLP), polymerase chain reaction (PCR) RFLP, PCRsequence-specific oligonucleotides (SSO) and PCR sequence-specificprimers (SSP). The value(s) should fall within predetermined levels as adeterminant of autoimmune thyroiditis.

Test panels Nos. 1, 2, 3 and 10 set out below can be used to obtain datafor this Example 4.

Example 5 Mammary Cancer

Characteristics related to presence of or susceptibilty to mammarycancer of the animal are determined. Biological laboratory test datafrom a bodily fluid or tissue of an animal are analyzed. The test datarelate to estrogen (estradiol-17β), estrogen receptors, interleukin (IL)6, progesterone, and progesterone receptors. The value should fallwithin predetermined levels as a determinant of the presence of orsusceptibilty to mammary cancer.

Test panels Nos. 1, 2, 3 and 10 set out below can be used to obtain datafor this Example 5.

Example 6 Immune Surveillance

Characteristics related to the tissue environment of the eye and brain(ocular and blood-brain barrier) which are sites protected from thenormal immunologic surveillance mechanisms are determined. Biologicallaboratory test data from a bodily fluid or tissue of an animal areanalyzed. The test data relate to the soluble and cellular immuneinflammatory response mediators (cytokine and chemokine levels,immunoglobulin levels, and lymphycyte susbset markers). The value shouldfall within predetermined levels as a determinant of integrity ofprotected immune surveillance mechanisms.

Test panels Nos. 1, 3, 5, 6, 8, 9 and 10 set out below can be used toobtain data for this Example 6.

Example 7 Inherited Bleeding Disorders

Characteristics related to the tendency to bleed excessively aredetermined. Biological laboratory test data from a bodily fluid ortissue of an animal are analyzed. The test data relate to acomprehensive assessment of the hemostatic and coagulation function. Thevalue should fall within predetermined levels as a determinant of thepresence of bleeding disorder.

Test panels Nos. 1, 7, and 9 set out below can be used to obtain datafor this Example 7.

TEST PANELS

The following are some specific diagnostic test panels and specializeddiagnostic tests and test groups used to monitor health, morbidity,mortality and longevity of animals and animal families, and to predictthe potential risks of disease or disorder:

Test 1: Comprehensive Diagnostic Test Panel

Patient phenotypic descriptors and genotypic descriptors/background;complete blood count (CBC) and platelet count, platelet size, plateletmorphology; serum chemistry profile [e.g., AST (SGOT), ALT (SGOT),bilirubin (total, direct and indirect), alkaline phosphatase, GGT(GGTP), total protein, albumin, globulin, A/G ratio, cholesterol, BUN,creatinine, BUN/creatinine ratio, phosphorus, calcium, correctedcalcium, calcium/phosphorus ratio, glucose, amylase, lipase, sodium,potassium, Na/K ratio, chloride, CPK, triglyceride, osmolality];complete thyroid profile (total T4, total T3, free T4 (ED or other),free T3, T3 autoantibody, T4 autoantibody, TSH, thyroglobulinautoantibody); and urinalysis, urine culture, and sensitivity, ifindicated.

Test 2: Diagnostic Test Panels for Endocrine Function

Patient phenotypic descriptors and genotypic descriptors/background,plus any or all of selected tests from the following list:

-   -   1) Thyroid Function: total T4, total T3, free T4 (ED or other),        free T3, T3 autoantibody, T4 autoantibody. Molecular screening        for autoimmune thyroiditis including immunoglobulin receptors on        B-cells, T-cell receptors, and major histocompatibilty complex        (MHC) genes Class I and II allellic HLA, DLA, or equivalent        animal antigenic specificities (RFLP, PCR/SSO, PCR/SSP).    -   2) Adrenal Function: cortisol (basal and after stimulation with        ACTH, or serially after suppression with high or low-dose        dexamethazone); endogenous cortisol; and endogenous ACTH.    -   3) Reproductive Function: testosterone; estradiol-17β; relaxin        (pregnancy diagnosis); progesterone; luteinizing hormone;        estrone sulfate; follicle stimulating hormone; vaginal cytology        and/or culture; testicular cytology or biopsy; prostatic        cytology, biopsy or wash; screens for ovarian or testicular        remnants.    -   4) Pancreatic Function: amylase; lipase; glucose; glucagon,        trypsin-like immunoreactivity (TLI); insulin, fructosamine;        glycosylated hemoglobin.    -   5) Parathyroid Hormone Function: parathormone; ionized calcium.    -   6) Other Endocrine Function: aldosterone; 21 adrenal        hydroxylase; vanylla mandelic acid (VMA, for epinephrine and        norepinephrine metabolities).

Test 3: Diagnostic Test Panels for Immunologic Function

Patient phenotypic descriptors and genotypic descriptors/background,plus any or all of selected tests from the following list:

Antinuclear antibody (ANA)—if positive, run double stranded, singlestranded, speckled, anti-RNA levels; Coombs' testing (direct andindirect; elution or microbeads gel-test); rheumatoid factor; serumelectrophoresis—if abnormal, run immunoelectrophoresis, isoelectricfocusing, immunoblotting (Western, Northern, Southern blots);immunoglobulin levels (IgG, IgA, IgM, IgD and IgE); complement levels(C1, C1a, C1 esterase inhibitor, C3, C4, C5-C9); LE-prep testing; lupusanticoagulant (dilute Russell's viper venom test or dilutional inhibitortest); urine protein SDS-gel electrophoresis; fibronectin andanti-fibronectin antibody; flow cytometry with fluorescence activatedcell sorter (FACS, for leukocyte subsets and markers such as CD4⁺ andCD8⁺; leukocyte chemotaxis (leukocyte migration inhibition test,leukotrienes); cytokines including lymphokines and monokines(macrophage-derived) such as the interleukins (IL) [e.g. IL-6 regulatedby estradiol-17β, IL-8 acts as neutrophil chemotactic factor],interferons, tumor necrosis factor(s), leukotrienes, colony stimulatingfacors, transforming growth factor-beta and chemokines (inflammatorycytokines); anti-platelet antibody tests (serum, bone marrow);anti-megakaryocyte antibody tests (IFA, elution); and anti-leukocyteantibody tests (direct and indirect anti-neutrophil cytoplasmicantibody, antilymphocyte antibody, etc.).

Test 4: Diagnostic Test Panels for Gastrointestinal Function andNutritional Analysis

Patient phenotypic descriptors and genotypic descriptors/background,plus nutritional and food supplement past and current use, plus any orall of selected tests from the following list:

Serum nutrients and vitamin analysis; CBC as in Test 1; serum chemistryas in Test 1 plus magnesium and iron; urinalysis, urine culture andsensitivity, if indicated; urine fractional excretion; serum and urineamino acid analyses; serum cobalamin (vitamin B₁₂) and folate analysis;TLI [same as Test 2, 4)]; fecal flotation; Giardia screen, Clostridiumperfringens enterotoxin test; cryptosporidiosis test (FA); toxoplasmosistest; bile acids test (resting and post-prandial); fecal alpha-₁protease inhibitor activity. If any abnormalities are present, furtherinvestigation includes ion-coupled plasma emission spectroscopy (ICP)for mineral analysis, and electrophoresis.

Test 5: Diagnostic Test Panels for Inborn Errors of Metabolism

Characteristics related to presence of or susceptibilty to mammarycancer of the animal are determined. Biological laboratory test datafrom a bodily fluid or tissue of an animal are analyzed. The test datarelate to estrogen (estradiol-17β), estrogen receptors, interleukin (IL)6, progesterone, and progesterone receptors. The value should fallwithin predetermined levels as a determinant of presence orsusceptibilty to mammary cancer.

Patient phenotypic descriptors and genotypic descriptors/background,plus any or all selected tests from the following list:

Genetic screening tests including blood and urine analyses formucopolysaccharides, cerebrosides, glycogen-storage diseases,phenylketones, phosphofructokinase, mannosidases, combined and specificimmunoglobulin deficiencies/dysfunctions; skin and tissue biopsies;karyotyping for genotype determination; and DNA marker analyses.

Test 6: Diagnostic Test Panels for Paternity Testing and DNAFingerprinting

Patient phenotypic descriptors and genotypic descriptors/background,plus any or all selected tests from the following list:

Major histocompatibilty complex (MHC) Class I and II alleles [analysesof HLA, DLA, or equivalent animal antigenic specificities]; genotyping;gene mapping and fingerprinting.

Test 7: Diagnostic Test Panels for Hemostatic and Coagulation Function

Patient phenotypic descriptors and genotypic descriptors/background,plus any or all selected tests from the following list:

Platelet count, platelet size (blood slide, mean platelet volume),platelet morphology (light, scanning, and electron microscopy);prothrombin time; partial thromboplastin time; fibrinogen;fibrin-fibrinogen degradation products (D-dimer test); platelet functiontests (aggregation, release, clot retraction, whole blood aggregation,ristocetin cofactor); von Willebrand factor antigen and multimeranalysis; specific coagulation factor analyses (factors II, V, VII,VIII:C, IX, X, XI, XII, XIII); fibrinolytic tests (plasminogen, plasmin,antiplasmin, tissue plasminogen activator, dilute whole blood lysistest, euglobulin lysis test); anti-thrombin III test; circulatinganticoagulant tests; platelet factors 3 and 4 (heparin cofactor);protein C; protein S; kinin-kinogen tests; prekallikrein test;alpha₁-antitrypsin assay; alpha₂-macroglobulin assay; C₁ esteraseinactivator assay; anti-platelet antibody, and anti-megakaryocyteantibody tests (see Test 3).

Test 8: Diagnostic Test Panels for Vaccinal Antibody Status, and AdverseVaccine or Potential Adverse Vaccine Reaction

Patient phenotypic descriptors and genotypic descriptors/background,plus any or all selected tests from the following list:

-   -   1) Serology for Vaccinal Antibody: canine distemper, canine        parvovirus, canine coronavirus, canine parainfluenza virus,        infectious canine hepatitis virus, canine bordetella, canine        Lyme (borrelia), canine leptospirosis, rabies virus, feline        panleukopenia virus, feline leukemia virus, feline infectious        peritonitis virus, feline immunodeficiency virus, feline        calicivirus, feline herpesvirus, and equine herpes viruses        (I–IV), etc.    -   2) Adverse Vaccine Reaction: Same as Test 3, but especially CBC;        ANA; Coombs' test; platelet count, size, and morphology;        anti-neutrophil cytoplasmic antibody, marker for vasculitis;        complement tests; leukocyte chemotaxis tests; urine        protein/creatinine ratio; anti-platelet antibody; immunoglobulin        levels, especially IgG, IgA, IgM; flow cytometry (FACS)        leukocyte subsets; cell cytotoxicity analysis; cytokines,        especially chemokines; and complete thyroid autoantibody panel.    -   3) Potential (High Risk) Vaccine Reaction: especially for breeds        such as the Akita, Weimaraner, Standard poodle, Eskimo Dog,        harlequin Great Dane; CBC; ANA; platelet count, size and        morphology; complete thyroid autoantibody panel; cell        cytotoxicity analysis; cytokines; and immunoglobulin levels,        especially IgG, IgA, IgM;

Test 9: Diagnostic Test Panels for Infectious Diseases

Patient phenotypic descriptors and genotypic descriptors/background,plus any or all selected tests from the following list:

-   -   1) North America: Ehrlichia species (E. canis, E. risticii, E.        equi, E. platys, etc.); Rickettsia rickettsei (RMSF); Borrelia        species (Lyme disease); Bartonella species (B. henselae, B.        vinsonii, B. clarridgeiae, B. kochlerae); systemic fungal        diseases (Coccidioides spp, Cryptococcus spp, Histoplasma spp,        Blastomyces spp, Aspergillus spp, ringworm); mange mites        (Demodex, Sarcoptes, Chyletiella, etc.); enteric diseases        (Clostridium perfringens enterotoxin); protozoan diseases        (Toxoplasma spp.; Coccidia spp; Giardia spp); retrovirses        (feline leukemia virus, feline immunodeficiency virus, equine        infectious anemia virus, bovine leukemia virus, caprine        arthritis virus; Corona viruses (canine coronavirus, feline        enteric coronavirus, feline infectious peritonitis virus;        Babesia spp (B. canis, B. gibsoni); Dirofilaria spp (heartworm);        other parasitic diseases (fleas, ticks, roundworms, tapeworms,        hookworms, Strongyles and other intestinal parasites); and        Chlamydia antigen (PCR testing).    -   2) International: Same as above plus Leishmania spp; Trypanosoma        spp.; Anaplasma spp; Yersina pestis.

Test 10: Other Diagnostic Tests

Patient phenotypic descriptors and genotypic descriptors/background,plus any or all selected tests from the following list:

Pathology (anatomic, histological, cytologic, immunohistochemical,electromicroscopy, FACS); blood typing; bone marrow analysis andspecific immunohistochemical staining; RFLP and PCR testing (applicableto many of the above categories); IFA and FA testing; ELISA testing,cell cytotoxicity testing, cytokine testing (see Test 3, other cytotoxiccell and mitochondrial tests); markers of neoplastic and paraneoplasticchange (cancer); neurotransmitters including serotonin, thegamma-aminobutyric acid (GABA), the glutamate, the dopamine, theglycine, the aspartate, the acetylcholine, the norepinephrine, thehistamine, the substance P, the vasopressin, the vasoactive intestinalpeptide, the neurotensin, or the other neuropeptides; and amino acidprofiling.

Comprehensive and Cumulative Database for Animal Health

There is a dynamic method and system of managing the health care,well-being and nutritional requirements of dogs or cats. An example isset out for a dog. It can be equally applicable to a cat.

A data base relating to the dog species generally, and a data baserelating to a selected group, for instance, the breed, of the dog isused. Data is obtained relating to the particular dog subject, and thisdata includes laboratory test data, and ideally diagnostic laboratorydata relating to that dog. The database of the dog and the breed, forexample, is related to the data of the subject data of the dog by acomputer. There is then determined, based on this relationship, aregimen for the management and are of the dog subject.

The health care and well-being could include the nutritional managementor the health management or the lifestyle management. The data base ofthe selected group of the species is at least one of breed, age, sex,size, weight, performance use, or geographical location.

The nutritional regimen is at least related to the nutrient or caloriccomposition needed for the dog subject, or the food allergies and foodintolerances of the dog subject. The therapeutic intervention ormaintenance needs of the dog are at least one of drugs, nutraceuticals,liquid intake, holistic treatments or exercise.

The diagnostic laboratory test data is a comprehensive general healthprofile and selectively at least one selected diagnostic profiles for aselected subject. The laboratory data for the subject is ideallyobtained over time from the same laboratory. This is likely to enhancethe uniformity of the data, and render the determinations more accurate,and predictive of health, nutritional requirements, temperament, andlongevity.

The database of at least one of the species or the group is periodicallyupdated thereby to obtain cumulative data of the dog species or groupwithin the dog species. Both of these data bases generally should beused, and both should be updated to obtain the cumulative data. In somecases, only one of the data bases is used and/or one of them isperiodically updated.

The data of the dog subject is also periodically updated. Overall thereis obtained cumulative data of the dog subject, species or group. Theupdating picks up data drift or data trends within different populationsof the particular dog subject, the groups (for instance, breed) and thespecies (for instance, the dog generally as a species) over time. Thisallows for the review and oversight of the database so as to besubstantially or essentially current.

Enhanced health care and well-being management of the dog subject isobtained. Thus the data of the dog subject is compared to substantiallyor essentially current data. Similarly, by retaining a historical recordof the dog subject data and relating this to the updated databases, theaccuracy with which the management of the health care and well-being,and the nutrition design of nutritional requirements or therapeutic andmaintenance interventions is significantly enhanced. In this manner, forinstance the food, supplements, nutraceuticals and the like, can bemodified by additions and/or subtractions of components based on thedetermined relationship, since these cumulative and dynamic data basesand data analyte changes over time, whereby the determined relationshipis significantly enhanced. Management of the dog subject in one or allof these respects is dealt with a high level of precision andpredictability.

The computer is at least one of an expert system or interrelationshipprogram or network for determining data base and data relationships.This can be a system such as a neural network, or other statisticalsampling systems and networks, and is discussed in more detail.

The determination of the health care, well-being, nutritional or othertherapeutic requirements and suggestions for promoting and maintaininghealth of the dog is reported on a communications network including theInternet. There is a payment procedure for the report which is achievedthrough the Internet. This is discussed in more detail.

A more detailed explanation of the features is now described.

An initial database, from a recent temporal period made on a group ofhealthy dogs. will use physical characteristics, health history, andcomprehensive laboratory data of these dogs for a specific geographicarea such as the U.S.A. and Canada, but also other geographic areascould be used. Additional databases could be developed for othercountries. Generally the same laboratory is used to generate thedatabase. The temporal retrospective database will be augmented in anon-going fashion with prospective data that continues to accumulate overthe future testing years. Results will be analyzed from the temporalretrospective database and then will be periodically reanalyzed every6–12 months depending on the size of the database to search for anytrends or drift in the values of specific analytes over time.

This is an important database to accumulate because the presence ofdrift over time means that subsequent studies of the same or otheranimals, whether they be healthy or have diseases, disorders or changesin lifestyle, diet or other parameters including reproduction, orperformance use need to take such drift in the database into account inorder to accurately interpret the values obtained. Animals of specificbreed or type characteristics, size, age, weight, performance level,lifestyle, geographic location will then have their laboratory profilesand physical characteristics and health history entered into a databasethat will start from entry into the system and continue on a regularbasis over time, preferably at least annually. Also entered into thisdatabase will be puppies that will be tested for the first time at aboutsix months of age, pre-puberty, and then before puberty, preferably inanestrus females, and then annually thereafter in a comprehensive mannerto establish a cumulative laboratory database for the individual animal.

These data will also be put into a group-specific database for the breedcharacteristics or the activity characteristics or any other parameterthat is useful to group together for analytical purposes. This method ofgathering comprehensive and cumulative data will permit not onlyanalysis of individual animals, whether they be healthy or expressingsome stage of disease or disorder, but also will allow analysis of theirmembership in a group. When the group is analyzed it will provide adatabase for predictive laboratory value expectation for similar membersof the group. By developing these databases in a cumulative manner thetrends for particular analytes or groups of analytes predictive of organfunction, for example, can then be compared within individual animals,healthy or diseased, with that of the retrospective and prospectivehealthy animal database to look for differences in trends. Thosedifferences in trends, as well as differences in individuals or groupsof animals, can then be used as a predictor of health, disease andlongevity.

Once trends or changes are identified within individual animals orwithin the related groups of animals or within specific analytes orgroups of analytes from a database, this will permit intervention in amanagement and treatment perspective. The intervention can benutritional, can include the use of dietary supplements, use of specificnutraceuticals, and can include, of course, other conventional andalternative treatments and management of health care. The database sogathered, while primarily phenotypic in its laboratory analytical senseand its patient descriptive sense, will also be predictive for the mostpart of the genotype of the individual animals or groups of animals inthe population, because the canine genome has changed very little overthe last hundred years, and so the majority of the canine genome isidentical between dogs, breeds and individuals. Differences in phenotype(physical appearance and size and weight, for example) within dog breedsconstitutes a very small genetic variation, less than 1%, within theoverall genome. Predicting genotype and phenotype with thesecomprehensive and cumulative laboratory test panels permits a novelapproach to intervening in the management and treatment of caninedisease and disorders and also in the maintenance of canine health andlongevity.

The comprehensive cumulative database developed with this inventionallows one to look at very early subtle changes that are consistentwithin individuals or groups of related individuals, animals within arelated group so that one can predict disease sooner, make interventionsthat are less expensive, less invasive, and more effective, and therebyreverse the process before it becomes more serious clinically.

One of the most effective and least invasive or harmful ways tointervene in promoting animal health and longevity would be to utilizedietary management. Specifically, wholesome foods are the key to abalanced functioning immune system and the resistance to disease. Giventhe tight database that is developed by this approach, extraneous noisein the results of comprehensive laboratory analyses is minimized. Onecan take the findings then for individual animals or groups of animalshaving cumulative laboratory evidence of trends or drift from the normalranges and design specific dietary interventions that will rebalance thesystem and promote immunological function and resistance to disease.This method of identifying what changes could be made in dietarycomponents or supplements does not depend on single point in timeindividual pet or other animal data, but in fact the key is developing acumulative comprehensive database over time for normal animals in alike-group location or activity level, as well as specific animalswithin the group in order to determine what trends are evidenced overtime and thereby use the trend to give a more solid determination ofwhat these changes in nutritional requirements or nutritionalsupplements or other intervention should be.

An example of the comprehensive diagnostic testing used in thisinvention is shown by the test panels in the application labeled as“Test One Comprehensive Diagnostic Panel”, and then there are selectedexamples for diagnostic panels that look at specific organ functions,such as endocrine function, immunological function, gastrointestinalfunction and nutritional analysis, and inborn errors of metabolism. Aspecific example could be the diagnostic test panel for thyroid functionwhich depends upon the comprehensive diagnostic test panel and then morespecific tests focused on the thyroid, including molecular-based testingand genomic mapping.

In a practical application on a large scale, the comprehensiveindividual and group databases that relate to thyroid function andanimal behavior are important. As the key to having an individual animalbecome a successful companion animal or member of a household, thesocial interaction of the animal with the caregivers is crucial. If theanimal has an undesirable behavior or social bad habits, very likely theanimal will be isolated, stressed, and may be treated unkindly and evenostracized by some family members, so that the animal may eventually begiven up or even sent to a pound and sheltered and be euthanized. Ifkept by the family, the animal will likely undergo significant stresswhich would contribute to immune suppression and lack of well-being andthus further promote the abnormal behavior. By using this database andidentifying animals that have very early subtle changes in laboratoryanalytes shown by their individual or cumulative data drift from theexpected normal parameters, one can intervene before the abnormalbehavior becomes unbearable for the family caregivers.

As a relationship for has been recognized between thyroid function andbehavior, early detection of thyroid imbalance allows one to intervene,specifically with nutritional support, and managing individualfoodstuffs and supplements that would optimize thyroid function beforethe disease progresses to the stage where thyroid hormone supplementbecomes an essential component of the management and treatment. Forinstance, food supplements containing kelp, iodine and the minerals fromgreen leafy vegetables could be very helpful in enhancing thyroidglandular output and function. Soybean-derived products by contrast tendto inhibit thyroid function, as can the quality and content of proteinin the diet. Because the thyroid is a major master gland that controlsthe metabolism of so many functions in the body, being able to balanceit with optimum nutrition would be extremely important because thyroiddisorder is the most common endocrine dysfunction amongst companionanimals today.

As it is well known that specific breeds that are used for performanceevents can have quite different basal thyroid metabolism, for examplesighthounds and other coursing breeds vs. toy breeds or working breeds,it is important in the cumulative database to determine thesecharacteristics by comprehensive profiling expected of this group as awhole, so that the data for individual animals could be compared to thegroup. Values for this specific functional group by breed would then becompared to the entire database for the canine as a species and specifictrends over time would be developed relating to age and to environmentalinfluences. Once the specific determinants of the individuals and thegroup that they belong to have been made, the trends that have beenidentified would be used to modify and intervene to promote health andlongevity, specifically again with modifications to dietary componentsor supplements as well as other changes in lifestyle, includingexercise, group housing, individual housing and parameters that wouldpromote wellness and longevity.

The term “group” here has many different characteristics. It couldinclude, for example, a specific breed of canine, a specific purpose forwhich these canines are used, such as those who are purely companionpets in a home situation, performance animals for show conformation, forobedience, working trials, coursing trials, and for sheep herding andother herding purposes. It could also involve groups of animalsdepending on where they live—in a temperate climate, a warm or tropicalclimate, an arid desert climate, or a cold northern climate. It willinclude, of course, animals that live in urban and rural areas, animalsthat live near water, animals of various ages, intact or neutered, andfor reproduction. In other words, the term “group” is used in a verybroad sense here and can apply to any group that the user wishes toinquire of the database. Thus, the group is any selected subset of thehealthy or diseased or disordered animals within the entire database.

The determination of the interrelationships between individuals orgroups of individuals in the database can use any one of a number ofcomputerized or other methods of analysis, simple or complex, includingsuch things as neural networking or other kinds of relational technologyevaluative databases.

Summary

This invention utilizes comprehensive and cumulative data profiling in anovel way over time to allow one to predict the specific nutritionalmanagement interventions that will assist in the care and management ofthe very earliest stages of specific abnormalities or trends that havebeen identified in the health profile of animals, thereby extending andimproving their health and longevity. This is an unique approach toscientifically and medically determining by comprehensive and cumulativelaboratory profiling of individual animals and animals within specifieddefined groups to permit intervention in preventive and management andtreatment of general and veterinary medical health care. Specifically,this invention directs the outcome of the laboratory profiling tonutritional and nutritional supplement management of the specificidentified abnormalities and trends over time to accomplish this goal.This is not only important but also practical because nutritionalintervention and management is relatively inexpensive, non-invasive andeasily accepted by the pet owner and the veterinary professional makingthese recommendations.

Overall System

FIG. 1 is an overview of the web-based system to provide access to theinvented database management system. With this system multiple users,for instance, remote users 8, access the web site 4 using the Internet6. Each of the users 8 has a computer terminal with the appropriatesoftware for accessing Internet. The users 8 may be unknown to the webserver computers 10 and 12. Each user 8 is allowed to browse the website and explore how the system functions.

There are several aspects to maintain security of information maintainedin the database server 22 and a banking system 28. A firewall 20prevents any user 8 from accessing any of the components behind thefirewall 20. In this way the users 8 have access to the web servercomputers 10 and 12, but only have access to the database server 22through the firewall 20. The database server 22 maintains, among otherthings, various database fields with respect to each of the healthprofiles of subjects and the genetic information of a subject andgroups. The database 22 maintains the services with a designationassociated to determine what health assessment data and genetic data canbe browsed by the users 8. Each of the web server computers 10 and 12allow users 8 to view subject and group categories and actual servicesand data products which are available from the database.

The web server computers 10 and 12 can be identical and can beduplicated as additional load or growth on the system occurs. The webserver computers 10 and 12 share the responsibility for servicing theusers of the site. This arrangement provides for expandability of thesystem by merely adding additional web server computers as necessary.

Preferably, the system includes an appropriate computer terminal 24 forinterfacing with independent financial institutions which are connectedon-line via the serial connection 26 to the financial institutioncomputers 28. This allows automatic real time confirmation of the accessof health profile and genetic data services and products. Once a userrequires access to a product or service, the user goes through anidentification or registration process and the exchange of financialinformation to allow for credit or debit card payment of the purchase.This is verified, confirmed and authorized by the appropriate banksystem institution 28. Confirmation of the purchase or deposit of data,or a service is made by a mail server 34 which sends an E-mail to theuser 8 confirming the purchase or deposit. The mail server 34 allows formail to be received and sent out. Security of the various databases ismaintained. Alert messages are generated when an unauthorized access isattempted. Verification messages, authorization messages andconfirmation messages are generated as appropriate.

The database server 22 is also designed to interact with an inputcomputer 32 operated by a CDPR. A firewall 30 serves to preventunauthorized access to the database server 22 or to the input computer32. The input computer 32 can input health profile data and genetic datato the database, after appropriate access and/or passwords are enteredinto the system. Similarly, users 8 through their own computers can useappropriate access codes and passwords to access input data to thedatabase server 22. This is tightly controlled for security reasons. Thedata may only be added to an independent sub-database of the data server22, and only after scrutiny by the CDPR operator of the database throughinput computer 32, will this data from users 8 be subsequently added tothe main database server 22.

FIG. 2 is an illustration of the Internet and its use in the system ofthe invention. The Internet 6 is a network of millions of interconnectedcomputers 40 including systems owned by Internet providers 42 andinformation systems 44 such as America Online™. Individual or corporateusers may establish connections to the Internet in several ways. A useron a home PC 46 may purchase an account through the Internet provider42. Using a modem 48, the PC user can dial up the Internet provider toconnect to a high speed modem 50 which, in turn, provides a full serviceconnection to the Internet. A user 52 may also make a somewhat limitedconnection to the Internet through a system 20 that provides an Internetgateway connection 54 and 56 to its customers. The database 22 is alsoconnected into the Internet 6 through an appropriate modem or high speedor direct interface 58. The database 22 is operable and maintained bythe CDPR operator computer 60. Users of the databases of the inventionwould access the Internet in an appropriately selected manner.

FIG. 3 is a block diagram of an exemplary computer system 100 forpracticing various aspects of the invention. The computer system 100includes a display screen or monitor 104, a printer 106, a disk drive108, a hard disk drive 100, a network interface 112, and a keyboard 114.The computer system 100 includes a microprocessor 116, a memory bus 118,random access memory (RAM) 129, read only memory (ROM) 122, a peripheralbus 124, and a keyboard controller 126. The computer system 100 can be apersonal computer, such as an Apple computer, e.g., an Apple Macintosh™,an IBM™ personal computer, or a compatible, a workstation computer, suchas a Sun Microsystems™ or Hewlett-Packard™ workstation, or some othertype of computer.

Microprocessor 116 is a general purpose digital processor which controlsthe operation of computer system 100. Microprocessor 116 can be asingle-chip processor or can be implemented with multiple components.Using instructions retrieve from memory, the microprocessor 116 controlsthe reception and manipulation of input data and the output and displayof data on output devices.

Memory bus 188 is used by the microprocessor 116 to access RAM 120 andROM 122. RAM 129 is used by microprocessor 116 as a general storage areaand as scratch-pad memory, and can also be used to store input data andprocessed data. ROM 122 can be used to store instructions or programcode followed by microprocessor 116 as well as other data.

Peripheral bus 124 is used to access the input, output, and storagedevices used by computer system 10. These devices include the displayscreen 104, printer device 106, disk drive 108, hard disk drive 110, andnetwork interface 112. The keyboard controller 126 is used to receiveinput from the keyboard 114 and send decoded symbols for each pressedkey to microprocessor 116 over bus 128.

The display screen or monitor 104 is an output device that displaysimages of data provided by microprocessor 116 via peripheral bus 124 orprovided by other components in computer system 100. The printer device106 when operating as a printer provides an image on a sheet of paper ora similar surface. Other output devices such as a plotter, typesetter,etc. can be used in place of, or in addition to the printer device 106.

The disk drive 108 and hard disk drive 110 can be used to store varioustypes of data. The disk drive 108 facilitates transporting such data toother computer systems, and hard disk drive 110 permits fast access tolarge amounts of stored data.

Microprocessor 116 together with an operating system operate to executecomputer code and produce and use data. The computer code and data mayreside on RAM 120, ROM 122, or hard disk drive 120. The computer codeand data could also reside on a removable program medium and loaded orinstalled onto computer system 100 when needed. Removable programmediums include, for example, CD-ROM, PC-CARD, floppy disk and magnetictape.

The network interface circuit 112 is used to send and receive data overa network connected to other computer systems. An interface card orsimilar device and appropriate software implemented by microprocessor116 can be used to connect computer system 100 to an existing networkand transfer data according to standard protocols. As such he computersystem is connectable through an interface device with the Internet 6.

Keyboard 114 is used by a user to input commands and other instructionsto computer system 100. Other types of user input devices can also beused in conjunction with the present invention. For example, pointingdevices such as a computer mouse, a track ball, a stylus, or a tabletcan be used to manipulate a pointer on a screen of a general-purposecomputer.

The present invention in relation to the animal database management ofdata can also be embodied as computer readable code on a computerreadable medium. The computer readable medium is any data storage devicethat can store data which can be thereafter read by a computer system.Examples of the computer readable medium include read-only memory,random-access memory, magnetic data storage devices such as diskettes,and optical data storage devices such as CD-ROMs. The computer readablemedium can also be distributed over network coupled computer systems sothat the computer readable code is stored and executed in a distributedfashion.

Specific System

FIG. 4 illustrates a browser system for use with the database system ofthe invention. A browser goes through a number of preliminary screensand logic steps, and reaches a screen 60 entitled “Next Entry”. Thisscreen provides data details or information generally indicated as 62.Clicking on any of these categories allows the user to review databasedetails 64, data specific details as generally indicated by 66. In thisway, the user can index through a number of screens to get informationregarding the different databases of the system. In addition, clickingon any of the triggers 70, 72, 74 and 76 is possible. These correspondto HOW IT WORKS, SECURITY, EXTENDED DATA and PRE-REGISTRATION. Clickingon trigger 70 provides the user with information on how the processworks, explains the system, and provides details on how the user canparticipate in the database and obtain data or input data. Clicking ontrigger 72 provides details regarding security of the system andautomatic payment. In some cases, products and services are offered withextended data and clicking on trigger 74 which can provide details ofthe extended data and explains that this may only be available oncertain services or products.

Trigger 76 allows a user to pre-register and obtain user ID number. ThisID number is combined with financial information retained in thedatabase in an encrypted form. The pre-registration trigger 76 followswith step 78 which is to gather personal information such as credit cardnumber and expiry date to allow for automatic payment. Step 80 is tovalidate a current existence in the database, if this occurs. With anegative answer, the user is directed into a registration processindicate as 82. A user ID is assigned and a password is entered. Thisinformation is maintained in a portion of the database 22. At 84 theuser is provided a screen identifying the user ID at screen 86. If theuser already exists, the registration process is rejected at 88 and theuser is advised of the information at the display 86. The screen at 86would also represent the information which is available in the database22.

In FIG. 5 there is shown a basic block diagram of the components makingup the CDPR. There is the phenotype database or physical health database200 and a genotype database or genetic information database 201. Theseare contained in part of the overall CDPR database 202. User input 203can be obtained from a remote user such as a veterinarian, owner,breeder, or the operator of the database, an agent or researcher. Theoutput from the database 204 could be to the veterinarian, owner,breeder, operator, agent or researcher.

FIG. 6 shows a relationship for retrieving data from the database 202.The user 8 is represented here as a veterinarian, owner, breeder,operator, or researcher 203 who accesses the CDPR 202 accesses a firstscreen through a computer network 6 which inquires about informationabout the user. An access request message is sent, and an appropriateaccess enabling message is transmitted. The user 203 can obtain partialor full access to the CDPR 202 according to the scale of authority givento the user 203 to access data. There is a computer program system 205to ensure that payment is made as appropriate before access to the CDPR202 is granted. In some situations, the appropriate access code 204 canpermit bypassing the payment requirement 205 as indicated by line 206.Payments 205 through the computer program can be effected by a creditcard entry and automatic transfer to a financial institution on behalfof the operator of the CDPR 202. Such payment for access to the databaseis effected by a system which is well known in the art. The financialinstitution will appropriately credit the operator of the CDPR 202 in afinancial manner as established between the operator and the financialinstitution.

Within the CDPR 201 there is the ability to access the physical healthphenotype database 200, the genotype database 201, and other databases207, 208 and 209, respectively. The phenotypic and genotypic informationtogether with other database information can be presented on a singlescreen or monitor or other viewing means, for instance, hard copyformat. The access therefore can be to multiple databases containedwithin the CDPR 202. After accessing the physical health database 200,the user obtains an analysis report from module 210. The user is thenable to read the analysis as indicated by 211 and output the analysisfrom the read-out 211 as indicated by output 212. The output 212 can bea computer screen read-out, fax or voice information.

The physical health or phenotype database 200 is subject or groupspecific. In other words, the data obtained in that database is specificto a particular animal or animal group (breed, family, species, etc.)which has been the subject of a laboratory or research biologicalexamination such that fluid or tissue samples have been subject toanalysis in one or more laboratory or research environments. Thesebiological reports can include those from specimens of blood, urine,other body fluids, skin, eyes, skeletal and other tissues. The PTdatabase 200 has the ability to store the subject specific informationas required within the CDPR 202.

The genotype specific or genetic disorder or disease data is retained inthe database 201 within the CDPR database 202. This data is eithersubject specific, family specific, breed specific, species specific,disorder specific, or disease specific, and is group or subjectspecific. The user can access the genotype database 201 and obtain aread-out 213 which can then be transmitted along line 214 to an output212 in the same manner that the physical health assessment is obtainedas an output.

In an alternative approach, the reader can request an analysis 215 fromthe genotype database as indicated by line 216. This analysis canreceive data along line 217 from the analysis information of thephysical health assessment. Interpretation of the PT and GT can beobtained as indicated by 218, and this can then be outputted asindicated along line 219. The interpretation of PT and GT 218 can beperformed by an algorithm relating to the coefficients andpredictability of information relating to disorders, disease andlongevity when considering the data from the two databases PT 200 and GT201. This can be done automatically and outputted along line 219, orthere can be an expert interface 220 using skilled personnel tointerpret the data of block 218, and this can, in turn, be outputtedalong line 221 to the output 212.

Database 207 can be a genetic marker database, and the information fromthat database can be directly input into the output through a read-out222 and 223 to the output 212. Alternatively, the data from database 207can be added to the interpretation section 218 of the physical healthand genetic information by directing the data along line 224. This datacan then be made the subject of the output along the line 219 and 221 asrequired.

Similarly other databases 208, 209, respectively, have read-outs 225 and226 which can be directly coupled along lines 227 and 228 to the output,or can be directed optionally along lines 229 and 230 to theinterpretation module 218. It can then be the subject of interpretationfor an expert interface 220 review which is, in turn, made the subjectof the output 219 and 221.

In each of the output lines 219, 221, 222, 223, 227, 228, and 214 thereis also provided an encryption program 231 which can be optionally usedin the system. The output 212 can include paper, electronic, or voiceread-out as is required.

In this manner, the output 212 provides a compilation which combines thephysical health and genetic information relating to a subject, thebreed, disease, disorder and lifespan, thereby enabling the receiver ofthe output 212 to use the compiled information in a manner to facilitatebreeding criteria which can be important in relation to animals whichare usually inbred or line bred. The information can also be used tofacilitate on-going monitoring of particular subject animals. The datafrom this system can be used to manipulate and regulate breeding,health, and longevity effectively among animals.

The system of the invention is further described with regard to FIG. 7which is a system for inputting data to the CDPR 202. Here multipleusers 203, which can be a remote user such as a laboratory, a breeder,an owner, hospital, agent, or an operator of the CDPR 202 accesses thesystem through module 204 which, in turn, accesses the CDPR 202.Appropriate access request and access enable messages are sent. Withinthe CDPR 202 there is a physical health or phenotype module 200, agenetic or genotype data module 201, and other database modules 207,etc. After accessing the CDPR 202, additional data can be added to themodules 200, 201, 207, etc. through any of the users 203, if authorized.Depositing data into each of the modules 200, 201 and 207 can optionallyrequire the payment to the operator of the CDPR 202 as is indicated byblock 205. This system can function in the same manner as the retrievalof data from CDPR 202.

The stored data in each of the blocks 200, 201, and 207 can be set up asindicated by block 232 in a manner which is restricted or unrestrictedto selected users 203. This may be necessary according to the protocolsgoverning the inputted data to the different databases. In some cases,the waiving of deposit fees is made in the interest of freedom of thedatabase to subsequent users who wish to retrieve data from thedatabase. After storage of the data as indicated by block 234, the user203 exits CDPR 202 as indicated by block 233.

As is apparent, the physical health or phenotype profile of subjectanimals is dynamic and grows as more data is added into the system.Likewise, the genetic genotype database also grows as increasingresearch of particular subjects, breeds, and the like is obtained. Thedeposit of new information into the CDPR 202 is regulated in a mannerthat the data cannot distort the databases 202 in an in appropriatemanner. Likewise, users 203 cannot access the secured databases withinCDPR 202 in an inappropriate manner.

Different algorithms regulate the relationship between the healthprofile, the genetic data, and other data relating to animals. Thesealgorithms determine the probabilities, possibilities, and likelihood ofdisorders and disease in subject animals and offspring animals. They areused as predictors of the future evolvement of health of the animal.

Examples of Inter-Relationship and Algorithm Inter-Relationship of thePhenotype and Genotype Data Bases

In one example the genetic influence on behavior and behavioraldisorders accounts for less than half of the phenotypic expression ofbehavior and behavioral differences. However, behavior is the mostcomplex phenotype, because it reflects not only the functioning of thewhole being but also is dynamic and changes in response to environmentalinfluences. These results are most dramatically seen in purebred animalsbecause they have been inbred and line-bred to select for a particularbehavior and conformation, even though the genotype of purebred breedsshows almost no variation over 100 years. Examples of this are all thedifferent purebred dog breeds which currently exist, and have widelydisparate size, weight, temperament and lifespans.

Accordingly, if the results of a mostly phenotypic database indicateabnormal thyroid function, then by relating this to the mostly genotypicand combined database categories of breed, age and sex, it is possibleto determine whether the subject has or does not have heritable thyroiddisease, or is likely to develop this condition within a predictedperiod of time.

Similarly, if the phenotypic database indicates elevated blood and urineglucose levels, then by relating this to the genotypic and combineddatabase categories of weight, age, sex, breed and reproductive history,it is possible to determine that the subject has diabetes that is likelyto be of an heritable basis.

Another example relates the phenotypic database indicating low blood vonWillebrand factor level to the genotypic and combined databasecategories of breed, age, sex, and clinical and family history, wherebyit is possible to determine whether the subject has the inherited oracquired form of von Willebrand disease.

Analyzing the data from the CDPR 102 in the manner of the presentinvention permits for genetic screening, health assessment profiling,and the diagnostic, prophylactic, and therapeutic management of animals.

An exemplary server performs all the operations of a conventionaldatabase system and performs additional operations in accordance withthe present invention as has been discussed. The server includes acentral processing unit (CPU) together with associated memory forprocessing information about different animals species and history. Theinquiries concern animals species and history and inquiries and requestsfor health profiling and genetic information, and providing healthprofiles and genetic information. The CPU is coupled to the database andto users via a communications port. The CPU is also coupled to anelectronic mail processor for processing and storing (in a storagedevice) e-mail messages transmitted between the CPU and various agents,users and the like. The CPU is further coupled to a data storage device.A data storage device may include a variety of the databases. The systempermits for the requesting, storing and providing of data with respectto animal phenotypic information and genetic information. The format andcontent of the databases have been discussed in detail.

FIG. 8 presents an overview of the laboratory instruments apparatus,system, and method operable with the present invention in relation to aCDPR 202. The present invention allows access by remote users withcomputers or processors 100 to receive and access data on specimens.Using the Internet 6 or other computer network or communication linkcapability, the remote user 8 sends a message to request access to theservices provided by the laboratory or operator which has a CDPR 202. Ifaccess to the CDPR 202 is granted, a message is sent to the remote usercomputers 100. This message includes instructions enabling the remoteuser 8 to define and access data stored in the CDPR 202.

In one form of the invention, the desired data is based on thesubmission of test specimens of a specific animal to the laboratory. Insome other cases health profile test data 200 can be inputted into theCDPR 202 having the genetic database 201. The CDPR 202 can perform ananalysis and correlation between the health profile database 200 and thegenetic database 201.

Using the communications link, the remote user 8 communicates with thelaboratory or the CDPR 202. Specimens can be packaged and physicallytransported to the laboratory site via commercially available commoncarriers, such as the postal service or courier services. When thepackages arrive, the laboratory places them in storage, or the tests areperformed. Instruments 300 perform the tests to obtain data as specifiedby the remote user 8. The biohazardous samples can be disposed of awaste material. The test results, or output is provided as part of ahealth profile database 200 of the CDPR 202 and is available to theremote user 8.

If desired, the remote user 8 can arrange to have the data stored in theCDPR 202, made available to other remote users 8. The remote user 8 canalso request the laboratory to perform analysis on the health profiledata 200 generated.

In one embodiment, the communications link is a computer network and themessage transfer modality is, for instance, the Internet 6, and/or anIntranet and/or an Extranet. The network systems are particularly suitedto the application described herein since it offers global or widespreadaccessibility and high speed data transfer of large amounts ofinformation.

A security unit allows remote users to designate who has permission toview or use their data. Feasible options for these informationmanagement requirements include: access by the submitting remote usersonly, access by certain designated researchers and collaborators,time-embargoed data followed by wider access, and unrestricted access byall.

A commerce unit can implement functions related to the business aspectsof the CDPR facility, including billing, inventory management of supportmaterials.

A multimedia unit comprises means to store, manipulate, and presentaudio, graphical, video information. This information may include avideo explaining how the CDPR is used, a visual depiction of the data,methodology, or a comment regarding the background of the data. Themultimedia unit may also implement subscription functions, so thatupdated data automatically provided to remote users or other interestedparties.

The operations performed by the present invention begins when thecontroller receives an access request message from the remote user via acommunication link. Using information in the access request message andany other available information, the controller determines if the remoteuser is authorized to access the CDPR 202. If so, an access enablingmessage is transmitted from the controller to the remote user 8. Theaccess enabling message can comprise a set of computer instructionstransmitted over the Internet 6 which is downloaded into the remote usermemory for execution by the remote user processor. These instructionsmay be enabling, that is, they may allow direct communication betweenthe remote user 8 and the CDPR 202 with no further need for thecontroller. In another embodiment, the access enabling message maysimply comprise a password or other enabling message which allows theremote user 8 to proceed. The remote user 8 can access or submit data tothe CDPR 202 according to different protocols and regimes and securityarrangements.

Different forms of expert system computing and software programming canbe used to determine the relationship of the data bases and data.Parallel distributed processing, and neuromorphic systems, such asneural networks can be used. They are good pattern recognition enginesand robust classifiers, with the ability to generalize in makingdecisions about imprecise input data. There are multitudes of differenttypes of networks such as a multilayer perceptron which is generallytrained with the backpropagation of error algorithm, learning vectorquantization, radial basis function, Hopfield, and Kohonen. Some arefeedforward while others are recurrent (i.e., implement feedback)depending on how data is processed through the network. Some may requiretraining while others are unsupervised or self-organizing. This can beimplemented in software or in specialized hardware.

Alternatively or additionally fuzzy logic can be used due to the dynamicnature of the data applications, rules and functions. Such logic isadaptive to the changing environment. This logic and the neural networkscan be integrated in the system.

Adaptive Logic Networks technology is an effective alternative oradditional technology. The Adaptive Logic Network is neurocomputingcapable of modeling complex non-linear systems by using piece-wiselinear data. The inputs to an Adaptive Logic Network may be the datafrom large databases as described, observations recorded by a scientist,veterinarian or owner. The outputs of an Adaptive Logic Network can beused for analysis, prediction, or real-time management.

Conclusion

As is clear the tests above which relate to at least one of endocrinefunction, immunologic function, gastrointestinal function andnutritional analysis, metobolism, paternity, DNA fingerprinting,hemostasis and coagulation function, vaccinal antibody status, adversevaccine reaction, infectious disease, pathology, anatomic, histological,cytologic, immunohistochemical, electromicroscopy, FACS, blood typing,bone marrow analysis and immunohistochemical staining, and allergyreaction about the animal provide useful information. This is in amanner previously not obtained.

As the above demonstrates, there is a need for providing data analysisand dissemination services to a wide variety of globally-distributedremote users. There is a need for providing a system for inputting,storing and retrieving data related to animal health assessment andgenetics in a manner which permits for the effective use of thisinformation.

The system also permits for the access to the genetic and/or phenotypedata through a password and a system whereby access to the datagenerates a fee. This system permits for the access or to provide datawith regard to credit cards or the like to ensure that the fee istransmitted automatically to a banking system for the account of thedatabase when such data is accessed.

This system also provides for a situation wherein payments can be madeby credit card for requests to perform health assessment profiles andsecure genomic mapping and genetic screening information. Suchbioinformatics system can also permit for the automatic payment for suchservices and products to the banking system of the database orlaboratory. As such, the database may require that the payments beguaranteed, for instance by supplying a credit card number with arequest for performance of services and a product, and for the retrievalof such data.

A user can submit a request to the database in any number of ways. Forexample, the request can be submitted via on-line direct connection,namely through a computer network such as the Internet. An intermediateresearcher such as a veterinarian or scientist other than the ownercould also submit the request on behalf of the owner using the e-mailcapabilities of the central database system. Alternatively, the user cansubmit the data via an interactive voice response unit coupled to thedatabase system of the supplier. In some situations, the databasesupplier can decide whether to supply the health assessment informationand/or genomic mapping and genetic screening information based on thecriteria of the user or its intermediary agent. Such user orintermediary agent can be notified of the decision via the interactiveresponse unit or a live operator.

The user or agent can log into the database system and obtain thenecessary records relating to an animal physical health and/or geneticancestry or offspring. The database system can transmit in real time oron a periodic basis as determined, thereby, providing informationregarding the health assessment or the genetic background and forwardthis information to the user and/or its intermediary agent.

The data storage devices of the invention include a variety of databasesincluding a database relating to the phenotypic data of a particularspecies, a database relating to health assessment or other phenotypicdata of particular animals in a particular species, and geneticcharacteristics of different species and different family trees relatingto different species. The family trees would contain informationincluding the origin, genomic map, and parental lines of a species andrecords of health and performance of a species. These databases areinterrelated in an analytical manner and in accordance with differentalgorithms of permutations and probabilities to facilitate useful outputinformation based on the combination of data in the genotypic and thephenotypic databases, and the selected databases.

Many other examples of the invention exist, each differing from othersin matters of detail only. The invention is to be determined solely bythe following claims.

REFERENCES

-   Dodds, W. J. More Bumps on the Vaccine Road. Adv. Vet. Med.    41:715–732, 1999.-   Canine Health Conference 1997, National Parent Club of American    Kennel Club/AKC Canine Health Foundation. Can. Pract. 23(1):1–56,    1998.-   Ru, G, Terracini, B, Glickman, L. Host Related Risk Factors for    Canine Osteosarcoma. Vet. J. 156:31–39, 1998.-   Glickman, L, Glickman, N, Schellenberg, D, et al. Multiple Risk    Factors for the Gastric Dilatation-Volvulus Syndrome in Dogs: A    Practitioner/Owner Case-Control Study. J. Am. Anim. Hosp. Assoc.    33:197–204, 1997.-   Patronek, G, Waters, D, Glickman, L. Comparative Longevity of Pet    Dogs and Humans: Implications for Gerontology Research. J. Gerontol.    52A:B171–178, 1997.-   Dodds, W. J. Autoimmune Thyroiditis and Polyglandular Autoimmunity    of Purebred Dogs. Can. Pract. 22 (1): 18–19, 1997.-   Hancock, W. W. Chemokines and the Pathogenesis of T Cell-Dependent    Immune Responses. Am. J. Pathol. 148: 681–684, 1996.-   Dodds, W. J. Estimating Disease Prevalence with Health Surveys and    Genetic Screening. Adv. Vet. Sci. Comp. Med. 39: 29–96, 1995.-   Happ, G. M. Thyroiditis—A Model Canine Autoimmune Disease. Adv. Vet.    Sci. Comp. Med. 39: 97–139, 1995.-   Merrill, J. E., Jonakait, A. G. M. Interactions of the Nervous    Systems in Development, Normal Brain Homeostasis, and Ddisease.    FASEB J. 9: 611–618, 1195.-   Cavallo, M. G., Pozzilli, P., Thorpe, R. Cytokines and Autoimmunity.    Clin. Exp. Immunol. 1: 1–7, 1994.-   Patronek, G. J., Glickman, L. T. The Epidemiological Approach to    Risk Management: Factors which Increase Chance of Disease. Vet.    Forum 11(8); 66–67, 1994.-   Jackwood, M. W. Biotechnology and the Development of Diagnostic    Tests in Veterinary Medicine. J. Am. Vet. Med. Assoc. 204:    1603–1605, 1994.-   Dodds, W. J., Raymond, S. L., Brooks, M. B. Inherited and Acquired    von Willebrand's Disease. Parts 1–2. Vet. Pract. STAFF 5(4–5): 1,    14–17; 21–23, 1993.-   Stefanon, G., Stefanon, B., Stefanon, G. G., Dodds, W. J. Inherited    and Acquired Bleeding Disorders in Northeastern Italy. Can. Pract.    18(3); 15–23, 1993.-   Dodds, W. J. Genetically Based Immune Disorders: Autoimmune and    Other Diseases. Parts 1–3. Vet. Pract. STAFF 4(1–3): 8–10, 1, 26–31;    35–37, 1992.-   Dodds, W. J. Genetically Based Immune Disorders: Immune Deficiency    Diseases. Vet. Pract. STAFF 4(5); 19–21, 1992.-   Brooks, M. B., Dodds, W. J., and Raymond, S. L. Epidemiologic    Features of von Willebrand's Disease in Doberman Pinschers, Scottish    Terriers and Shetland Sheepdogs. 260 cases (1984–1988). J. Am. Vet.    Med. Assoc. 200:1123–1127, 1992.-   Dodds, W. J. Autoimmune Thyroid Disease. Dog World 77(4): 36–40,    1992.-   Dodds, W. J. Unraveling the Autoimmune Mystery. Dog World 77(5):    44–48, 1992.-   Dodds, W. J. Thyroid Can Alter Behavior. Dog World 77(10):40–42,    1992.-   Goetzl, E. J., Sreedharan, S. P. Mediators of communication and    adaptation in the neuroendocrine and immune systems. FASEB J. 6:    2646–2652, 1992.-   Elmslie, R. E., Dow, S. W., Ogilvie, G. K. Interleukins: Bilolgical    Properties and Therapeutic Potential. J. Vet. Int. Med. 5: 283–293,    1991.-   Raymond, S. L., Jones, D. W., Brooks, M. B., Dodds, W. J. Clinical    and Laboratory Features of a Severe Form of von Willebrand's Disease    in Shetland Sheepdogs. J. Am. Vet. Med. Assoc. 197:1342–1346, 1990.-   Patterson, D. F., Haskins, M. E., Jezyk, P. F., Giger, U. et al.    Research on Genetic Diseases:Reciprocal Benefits to Animals and    Man. J. Am. Vet. Med. Assoc. 193: 1131–1144, 1988.-   Jolly, R. D., Dodds, W. J., Ruth, G. R., Trauner, D. B. Screening    for Genetic Diseases: Principles and Practice. Adv. Vet. Sci. Comp.    Med. 25: 245–276, 1981.

1. A method of analyzing the health profile of a non-human animal comprising: a) providing a phenotypic and a genotypic database to the species of the non-human animal subject or a selected group of the species; obtaining animal data; c) correlating the databases of a) with the data of b) to determine a relationship between the database of a) and the data of b); and d) determining the health profile of the animal based on the correlating step.
 2. The method of claim 1, wherein the data to the animal are data obtained from analyzing bodily fluid or tissue.
 3. The method of claim 2, wherein the data are metabolic components.
 4. The method of claim 3, wherein the metabolic components are amino acids, carbohydrates, or lipids.
 5. The method of claim 1 including the step of reporting the determination on a communications network including the Internet.
 6. The method of claim 1 including the step of reporting the determination on a communications network including the Internet, and obtaining payment for the report through the Internet.
 7. A method of determining a nutritional regime for a non-human animal comprising the steps of: a) providing a phenotypic and a genotypic database to the species of the non-human animal subject or a selected group of the species; obtaining animal data; c) correlating the databases of a) with the data of b) to determine a relationship between the database of a) and the data of b); and d) determining the nutritional regimen for the animal based on the correlating step.
 8. The method of claim 7, wherein the data to the animal are data obtained from analyzing bodily fluid or tissue.
 9. The method of claim 8, wherein the data are metabolic components.
 10. The method of claim 9, wherein the metabolic components are amino acids, carbohydrates, or lipids.
 11. A method of determining a nutritional regime for a non-human animal comprising the steps of: a) providing a phenotypic, a genotypic database, and a laboratory database to the species of the non-human animal subject or a selected group of the species; b) obtaining animal data c) correlating the databases of a) with the data of b) to determine a relationship between the database of a) and the data of b); and d) determining the nutritional regimen for the animal based on the correlating step.
 12. The method of claim 11, wherein the laboratory database is metabolic components.
 13. The method of claim 12, wherein the metabolic components are amino acids, carbohydrates, or lipids. 